Childbearing has experienced delays in Western countries in the last several decades. The proportion of births to women aged 30 years and above has risen to its highest level. Similarly, men also tend to defer childbearing to older ages. We believe that there will be measureable effects of parental age at birth on the health of offspring. The immediate effects of advanced maternal age (e.g., chromosomal abnormalities) and paternal age (e.g., Apert syndrome and achondroplasia) on the health of offspring have been extensively studied. In addition, recent studies have shown that increased paternal age at birth is associated with childhood and adolescent disorders such as schizophrenia, childhood leukemias and nervous system tumors. However, the effects of parental age at birth on the risk of adult-onset cancer have not been extensively investigated. To date, the association with parental age has only been studied for breast cancer, prostate cancer and hematological malignancies. Breast cancer risk is associated with both advanced maternal age and paternal age, but the risk of prostate cancer and hematological malignancies are only associated with advanced paternal age. Biological evidence of higher levels of circulating estrogens with advancing gestational age and higher chance of germ cell mutations and DNA damage from older fathers (but not older mothers) supports the possibility that advanced maternal age may increase the risk of hormone-related cancers; advanced paternal age may be a common risk factor for most types of cancer. Therefore, we aim to evaluate the independent effect of paternal age/maternal age on the risk of the 10 most common adult-onset cancers (not including non- Hodgkin lymphoma on which we have published) among U.S. women, accounting for the effects of birth order, socioeconomic status, and other potential cancer-specific risk factors in the California Teachers Study (CTS). The CTS, a prospective cohort study of 133,479 female California public school professionals, provides a unique opportunity for this aim because it contains both parental age information and an extensive list of potential cancer risk factors related to women's health and particularly to cancer risk. From 1995 through 2009, the incident cases for the specific cancers to be studied are 5007 (breast), 1017 (lung), 843 (colon), 279 (rectal), 1031 (endometrial), 298 (thyroid), 195 (kidney), 486 (ovarian), 337 (pancreatic) and 761 (melanoma). We will use multivariate Cox proportional hazards model to estimate the relative risks associated with maternal age and paternal age, considering cancer-specific risk factors for each cancer outcome. Successful completion of this project will address a gap in knowledge regarding the effect of parental age on adult-onset cancer risk. It will provide insight to further pursue the biological mechanisms between parental age and cancer risk. The long-term goal of the research is to explore biomarkers that link parental age and cancer risk to clarify etiology, and thus provide potential targets for prevention. PUBLIC HEALTH RELEVANCE: More and more couples defer childbearing to older ages in recent decades. Although the immediate effects of advanced parental age on the health of offspring has been extensively studied, its effect on adult-onset cancer risk has not been extensively investigated. By examining the effect of parental age on the risk of common adult-onset female cancers, this study will provide critical new knowledge to clarify cancer etiology and thus provide potential targets for prevention.